A transmission electron microscope is requested to be used by four PHS-supported projects. One of these projects includes an ultrastructural examination of the neurons involved in bladder function while the other three address issues of mammalian CNS regeneration. Project 1 (CM) examines the structural basis for urination and employs iontophoretic filling of sacral preganglionic neurons with horseradish peroxidase. One-third of this project will be devoted to an electron microscopic analysis of these neurons and the types of synaptic inputs they receive. The results of this project could benefit victims of spinal cord injury by providing insights into ways to restore lost bladder control. Project 2 (FL) looks at the role of astrocytes in inhibiting adult mammalian CNS regeneration. The model used is the adult mammalian dorsal root transitional zone where regenerating axons grow from a supportive PNS environment into an inhibitory CNS one. The major thrust of this project includes a detailed ultrastructural analysis of the interactions of growing axons with reactive astrocytes in this region of the spinal cord. Understanding how astrocytes stop axonal growth could lead to interventions that may promote axonal regeneration after human CNS injury. Project 3 (KS) asks whether CNS axons can innervate peripheral targets, thereby restoring motor and sensory function . While it has been shown that CNS axons will enter and grow in peripheral nerve grafts, it has not been clearly demonstrated whether these axons can establish a functional innervation of skin and muscle. This project combines neurophysiological and light and electron microscopic approaches. Reinnervation of peripheral targets could lead to ways of restoring sensation and some voluntary motor control to the body below the site of a spinal cord injury. 4 (KS) confronts Project questions of whether astrocytes may play a role in the remission of symptoms associated with multiple sclerosis. This project uses physiological techniques to evaluate axonal conduction through experimentally produced demyelinating lesions. Use of electron microscopy to establish a set of ultrastructural correlates that describe recovery of function is an essential adjunct to the physiological experiments as a way of characterizing the cellular constitution of the lesion sites, and the presence and type of any intracellular contacts. Data from this project will contribute to a better understanding of the cellular processes occurring within central demyelinating lesions and how these processes affect the course of disease such as multiple sclerosis.